DNA chips are tools for simultaneous multiple genetic analyses, simultaneous investigations of the presence of various types of mRNAs, or simultaneous multiple analyses of SNPs (single nucleotide polymorphisms) and are attracting much attention. A DNA chip is a probe array including periodically arranged probe-holding portions holding different types of probes including known DNAs hybridizing with target DNA or RNA molecules.
Antigen chips and antibody chips are also tools for simultaneous investigations of the presence of various types of antibodies and antigens and are attracting much attention.
An antigen chip is a probe array including periodically arranged probe-holding portions holding different types of probes including known antigens binding to target antibody molecules. An antibody chip is a probe array including periodically arranged probe-holding portions holding different types of probes including known antibodies binding to target antigen molecules.
A known method for manufacturing an ordinary probe array is as follows: a probe solution is trickled onto a base such as a glass slide such that probe spots are arranged on the base. Such a method is referred to as a spotting method. FIG. 15 shows a probe array, manufactured by the spotting method, including a glass slide 400 on which spots 401 of a probe solution are arranged. The spotted solution is finally dried such that probe molecules are adsorbed on the glass slide 400, whereby this probe array is obtained. Known examples of the spotting method include methods for discharging probe solutions from syringes, micropipettes, or ink jet nozzles onto bases and methods for providing probe solutions onto bases by bringing needles carrying these probe solutions into contact with these bases.
Patent Document 1 discloses a micropipette used to densely arrange micro-sized droplets by the spotting method. Patent Document 2 discloses a method for manufacturing an array base on which droplets supplied from a micropipette are efficiently arranged and which has a structure effective in preventing the contamination of the droplets.
Patent Document 1: Japanese Unexamined Patent Application Publication No. 2004-045055
Patent Document 2: Japanese Unexamined Patent Application Publication No. 2004-004076
Probe arrays preferably include various types of probes (probes holding different types of probe molecules or probes their selves) arranged in a predetermined area. That is, in the probe arrays, the number of the probes arranged in a unit area is preferably large.
There is a problem in that the spotting method is unsuitable for manufacturing a probe array with a sufficiently high degree of integration because spots of a probe solution spread on a base.
In order to solve the problem, the following techniques have been proposed: a technique in which frames for preventing such spots from expanding on a base are formed and a technique in which the expansion of such spots is prevented in such a manner that a hydrophobic pattern is formed on a base. However, the intervals between the spots are limited to about 150 μm even if these techniques are used.
The probes need to hold a sufficient number of probe molecules. When the number of the probe molecules held by the probes is insufficient, the number of target molecules binding to or hybridizing with the probes is insufficient; hence, it is difficult to detect the target molecules. In a high-integration probe array manufactured by the spotting method, spots have a small area and therefore the number of probe molecules in each spot is insufficient; hence, the ability of this array to detect the target molecules is low.
The number of the probe molecules held by the probes is preferably constant. This is because the number of the target molecules binding to or hybridizing with the probes varies when the number of the probe molecules held by the probes is not constant even if test solutions have the same target concentration. If the number of the target molecules binding to or hybridizing with the probes varies, the intensity of signals varies; hence, the concentration of the target molecules in each test solution cannot be precisely determined. The spotting method has a problem in that the amount of the probe solution spotted onto the base varies. That is, there is a problem in that the number of the probe molecules, which are adsorbed on the base after the probe solution is dried, is likely to vary. In the manufacture of a high-integration probe array, the amount of the probe solution spotted thereonto is very small and therefore the amount of the probe solution differs between the probes. This leads to a problem in that the number of the probe molecules varies significantly.